POGLUT1 Gene: Protein O-Glucosyltransferase 1 – Function, Mutations, and Associated Diseases
A comprehensive biomedical overview of POGLUT1, including gene card, expression, mutations, and clinical relevance.
Gene Information Card
| Symbol | POGLUT1 |
|---|---|
| Full Name | Protein O-Glucosyltransferase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q27.1 |
| NCBI Gene ID | 56983 ncbi.nlm.nih.gov/gene/56983 |
| Ensembl ID | ENSG00000163399 |
| UniProt ID | Q6N021 |
| OMIM ID | 615618 |
| HGNC ID | 22954 |
| Aliases | C3orf9, CLP46, hCLP46, MDS010 |
Description
POGLUT1 encodes protein O-glucosyltransferase 1, an enzyme localized to the endoplasmic reticulum that transfers glucose to serine residues of epidermal growth factor-like (EGF) repeats on Notch receptors. This post-translational modification is essential for proper Notch signaling, which regulates cell fate decisions, proliferation, and differentiation. Mutations in POGLUT1 are associated with autosomal recessive Dowling-Degos disease (DDD) and have been implicated in cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Dowling-Degos disease (DDD) | Loss-of-function mutations impair O-glucosylation of Notch receptors, leading to disrupted Notch signaling in skin keratinocytes, causing reticulate pigmentation. | ClinVar, OMIM (615618) |
| Cancer (various) | Altered POGLUT1 expression may affect Notch signaling, contributing to tumor progression; specific mutations may act as oncogenic drivers. | COSMIC (somatic mutations found in multiple cancer types) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Skin | High | High |
| Brain | Medium | Medium |
| Liver | Medium | Medium |
| Kidney | Medium | Medium |
| Lung | Medium | Medium |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| HeLa (cervical cancer) | High | Strong expression; used in functional studies |
| HepG2 (liver cancer) | Medium | Moderate expression |
| A549 (lung cancer) | Medium | Moderate expression |
| MCF7 (breast cancer) | Low | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.130G>A (p.Asp44Asn) | Missense | Rare (germline in DDD) | Loss of enzymatic activity; disrupts Notch signaling |
| c.491C>T (p.Pro164Leu) | Missense | Rare (germline in DDD) | Loss of function; reduced O-glucosyltransferase activity |
| c.1045C>T (p.Arg349Ter) | Nonsense | Rare (germline in DDD) | Truncated protein; likely loss of function |
| c.1010A>G (p.Glu337Gly) | Missense | Somatic (COSMIC) | Unknown; may affect protein stability or activity |
Mutation functional classification
Loss of Function (LOF)
Most POGLUT1 mutations in Dowling-Degos disease are loss-of-function, leading to reduced or absent O-glucosyltransferase activity, impairing Notch signaling.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression in some cancers may enhance Notch signaling, but this is not mutation-driven.
Dominant Negative (DN)
Not established; POGLUT1 mutations are typically recessive, requiring biallelic loss for disease manifestation.
View complete mutation data：
Gene Ontology (GO)
| • O-glucosyltransferase activity | • Notch receptor processing |
| • Endoplasmic reticulum lumen | • Protein O-linked glycosylation |
| • Regulation of Notch signaling pathway |
Pathways
• Notch signaling pathway
• Protein glycosylation pathway
Protein Summary
POGLUT1 is a 392-amino acid endoplasmic reticulum transmembrane protein that catalyzes the addition of glucose to serine residues within EGF-like repeats of Notch receptors. This modification is required for proper Notch receptor folding, trafficking, and ligand-induced activation. The protein contains a conserved DxD motif essential for catalytic activity. POGLUT1 is widely expressed, with highest levels in skin, and plays a critical role in development and tissue homeostasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| POGLUT1 Knockout HEK293 Cell Line | EDJ-KQ2006 | Human | 56983 | Details Get a Quote |
| POGLUT1 Knockout A-549 Cell Line | EDJ-KQ22023 | Human | 56983 | Details Get a Quote |
| POGLUT1 Knockout HCT 116 Cell Line | EDJ-KQ22024 | Human | 56983 | Details Get a Quote |
| POGLUT1 Knockout HeLa Cell Line | EDJ-KQ20724 | Human | 56983 | Details Get a Quote |
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